Type 2 Cytokine–Dependent Skin Barrier Regulation in Personalized 2-Dimensional and 3-Dimensional Skin Models of Atopic Dermatitis: A Pilot Study
Keratinocytes (KCs) from healthy donors stimulated with type 2 cytokines are often used to experimentally study atopic dermatitis (AD) inflammatory responses. Owing to potential intrinsic alterations, it seems favorable to use KCs from patients with AD. KCs isolated from hair follicles offer a nonin...
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Elsevier
2025-01-01
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| Series: | JID Innovations |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667026724000560 |
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| author | Hila Emmert Franziska Rademacher Matthias Hübenthal Regine Gläser Hanne Norsgaard Stephan Weidinger Jürgen Harder |
| author_facet | Hila Emmert Franziska Rademacher Matthias Hübenthal Regine Gläser Hanne Norsgaard Stephan Weidinger Jürgen Harder |
| author_sort | Hila Emmert |
| collection | DOAJ |
| description | Keratinocytes (KCs) from healthy donors stimulated with type 2 cytokines are often used to experimentally study atopic dermatitis (AD) inflammatory responses. Owing to potential intrinsic alterations, it seems favorable to use KCs from patients with AD. KCs isolated from hair follicles offer a noninvasive approach to investigate AD-derived KCs. To evaluate whether such AD-derived KCs are suitable to mimic AD inflammatory responses, we compared hair follicle–derived KCs from healthy donors with those from patients with AD in a type 2 cytokine environment. Stimulation of AD-derived KCs with IL-4 and IL-13 induced higher expression changes of AD-associated markers than that of healthy KCs. The combination of IL-4 and IL-13 generally induced highest expression changes, but IL-13 alone also induced significant changes of AD-specific markers. Similar to the 2-dimensional cultures, IL-4/IL-13 stimulation of 3-dimensional skin models generated with AD-derived KCs modulated the expression of several AD-relevant factors. Whole-transcriptome analysis revealed that IL-4 and IL-13 acted similarly on these 3-dimensional skin models. Histologically, IL-13 alone and in combination with IL-4 increased epidermal spongiosis, a histological hallmark of AD skin. Taken together, our pilot study suggests that hair follicle–derived KCs from patients with AD represent a useful model system to study AD-related inflammation in a personalized in vitro model. |
| format | Article |
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| institution | Kabale University |
| issn | 2667-0267 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JID Innovations |
| spelling | doaj-art-f9b8d10e86e64564b06ff0e18e29e03f2025-01-11T06:42:09ZengElsevierJID Innovations2667-02672025-01-0151100309Type 2 Cytokine–Dependent Skin Barrier Regulation in Personalized 2-Dimensional and 3-Dimensional Skin Models of Atopic Dermatitis: A Pilot StudyHila Emmert0Franziska Rademacher1Matthias Hübenthal2Regine Gläser3Hanne Norsgaard4Stephan Weidinger5Jürgen Harder6Department of Dermatology, University Hospital Schleswig-Holstein, Kiel, GermanyDepartment of Dermatology, University Hospital Schleswig-Holstein, Kiel, GermanyDepartment of Dermatology, University Hospital Schleswig-Holstein, Kiel, GermanyDepartment of Dermatology, University Hospital Schleswig-Holstein, Kiel, GermanyDepartment of Translational Sciences, Research & Early Development, LEO Pharma, Ballerup, DenmarkDepartment of Dermatology, University Hospital Schleswig-Holstein, Kiel, GermanyDepartment of Dermatology, University Hospital Schleswig-Holstein, Kiel, Germany; Correspondence: Jürgen Harder, Department of Dermatology, Quincke Research Center, Kiel University, Rosalind-Franklin Street 7, Kiel 24105, Germany.Keratinocytes (KCs) from healthy donors stimulated with type 2 cytokines are often used to experimentally study atopic dermatitis (AD) inflammatory responses. Owing to potential intrinsic alterations, it seems favorable to use KCs from patients with AD. KCs isolated from hair follicles offer a noninvasive approach to investigate AD-derived KCs. To evaluate whether such AD-derived KCs are suitable to mimic AD inflammatory responses, we compared hair follicle–derived KCs from healthy donors with those from patients with AD in a type 2 cytokine environment. Stimulation of AD-derived KCs with IL-4 and IL-13 induced higher expression changes of AD-associated markers than that of healthy KCs. The combination of IL-4 and IL-13 generally induced highest expression changes, but IL-13 alone also induced significant changes of AD-specific markers. Similar to the 2-dimensional cultures, IL-4/IL-13 stimulation of 3-dimensional skin models generated with AD-derived KCs modulated the expression of several AD-relevant factors. Whole-transcriptome analysis revealed that IL-4 and IL-13 acted similarly on these 3-dimensional skin models. Histologically, IL-13 alone and in combination with IL-4 increased epidermal spongiosis, a histological hallmark of AD skin. Taken together, our pilot study suggests that hair follicle–derived KCs from patients with AD represent a useful model system to study AD-related inflammation in a personalized in vitro model.http://www.sciencedirect.com/science/article/pii/S26670267240005603D skin modelsAtopic dermatitisHair follicle–derived keratinocytesIL-13IL-4 |
| spellingShingle | Hila Emmert Franziska Rademacher Matthias Hübenthal Regine Gläser Hanne Norsgaard Stephan Weidinger Jürgen Harder Type 2 Cytokine–Dependent Skin Barrier Regulation in Personalized 2-Dimensional and 3-Dimensional Skin Models of Atopic Dermatitis: A Pilot Study JID Innovations 3D skin models Atopic dermatitis Hair follicle–derived keratinocytes IL-13 IL-4 |
| title | Type 2 Cytokine–Dependent Skin Barrier Regulation in Personalized 2-Dimensional and 3-Dimensional Skin Models of Atopic Dermatitis: A Pilot Study |
| title_full | Type 2 Cytokine–Dependent Skin Barrier Regulation in Personalized 2-Dimensional and 3-Dimensional Skin Models of Atopic Dermatitis: A Pilot Study |
| title_fullStr | Type 2 Cytokine–Dependent Skin Barrier Regulation in Personalized 2-Dimensional and 3-Dimensional Skin Models of Atopic Dermatitis: A Pilot Study |
| title_full_unstemmed | Type 2 Cytokine–Dependent Skin Barrier Regulation in Personalized 2-Dimensional and 3-Dimensional Skin Models of Atopic Dermatitis: A Pilot Study |
| title_short | Type 2 Cytokine–Dependent Skin Barrier Regulation in Personalized 2-Dimensional and 3-Dimensional Skin Models of Atopic Dermatitis: A Pilot Study |
| title_sort | type 2 cytokine dependent skin barrier regulation in personalized 2 dimensional and 3 dimensional skin models of atopic dermatitis a pilot study |
| topic | 3D skin models Atopic dermatitis Hair follicle–derived keratinocytes IL-13 IL-4 |
| url | http://www.sciencedirect.com/science/article/pii/S2667026724000560 |
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